It is fairly well established that a clinical diagnosis of "fetal alcohol syndrome" (FAS) may be made in some babies of women who were heavy alcohol consumers during pregnancy. This syndrome consists of variable combinations of prenatal developmental deficiences, morphologic anomalies, aberrations in normal behavioral patterns and deficits in central nervous system development, including mental retardation. In previous studies we have developed a Beagle model of FAS by the intragastric administration of a six dose sequence of ethanol to different groups of pregnant Beagles throughout their gestation period of about nine weeks and observed the dose-effects relationships of this in utero ethanol exposure on their offspring. In these experiments a "critical dose range" was associated with reduction of normal fetal development, induction of spontaneous abortion, increasing frequency of stillbirths, underdevelopment of liveborn offspring, the occurrence of various structural abnormalities and birth defects, and with an increased incidence of early mortality of liveborn progeny. Current results indicate that the administration of a given "effective" dose of ethanol throughout gestation induces a wider spectrum of abnormalities and more severe disturbances in fetal development than when the same dose is given only during various short segments of gestation, including the period of organogenesis. Larger doses prevented the delivery of viable offspring or otherwise suppressed differentiation of fetal growth. Continuing work on this project involves the administration only during other segments prior to or within the gestation period of doses of ethanol which have been shown to disturb normal fetal development when given throughout gestation. Also, designs to represent "once daily" doses and "binge drinking" mimicry will be included. Other studies will involve measurement of reproductive hormones levels in the material circulation during ethanol administration and patterns of behavior in offspring. All effects are correlated with peak blood-ethanol concentrations in the pregnant animals, which reflect fetal ethanol levels also.